Longitudinal disease-associated gut microbiome differences in infants with food protein-induced allergic proctocolitis

Study information

Needs review

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

36138438

DOI Digital object identifier for electronic documents.

https://doi.org/10.1186/s40168-022-01322-y

URI

https://pubmed.ncbi.nlm.nih.gov/36138438/

Authors

Martin VM, Virkud YV, Dahan E, Seay HL, Itzkovits D, Vlamakis H, Xavier R, Shreffler WG, Yuan Q, Yassour M

Journal

Microbiome

Year

2022

BACKGROUND: Complex interactions between the gut microbiome and immune cells in infancy are thought to be part of the pathogenesis for the marked rise in pediatric allergic diseases, particularly food allergies. Food protein-induced allergic proctocolitis (FPIAP) is commonly the earliest recognized non-immunoglobulin E (IgE)-mediated food allergy in infancy and is associated with atopic dermatitis and subsequent IgE-mediated food allergy later in childhood. Yet, a large prospective longitudinal study of the microbiome of infants with FPIAP, including samples prior to symptom onset, has not been done. RESULTS: Here, we analyzed 954 longitudinal samples from 160 infants in a nested case-control study (81 who developed FPIAP and 79 matched controls) from 1 week to 1 year of age by 16S rRNA ribosomal gene sequencing as part of the Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) study. We found key differences in the microbiome of infants with FPIAP, most strongly a higher abundance of a genus of Enterobacteriaceae and a lower abundance of a family of Clostridiales during the symptomatic period. We saw some of these significant taxonomic differences even prior to symptom onset. There were no consistent longitudinal differences in richness or stability diversity metrics between infants with FPIAP and healthy controls. CONCLUSIONS: This study is the first to identify differences in the infant gut microbiome in children who develop FPIAP, some even before they develop symptoms, and provides a foundation for more mechanistic investigation into the pathogenesis of FPIAP and subsequent food allergic diseases in childhood. Video abstract.

Experiment 1

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Curated date: 2023/10/09

Curator: Tolulopeo

Revision editor(s): Tolulopeo, LGeistlinger

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: ulcerative proctosigmoiditis chronic ulcerative rectosigmoiditis (disorder),Proctocolitis,proctosigmoiditis,Proctosigmoiditis (disorder),ulcerative (chronic) proctosigmoiditis,ulcerative proctosigmoiditis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Infants diagnosed without food protein-induced allergic proctocolitis (FPIAP)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Infants diagnosed with food protein-induced allergic proctocolitis (FPIAP)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Infants diagnosed with food protein-induced allergic proctocolitis (FPIAP) who had a minimum of 4 longitudinal stool samples in the first year. FPIAP was diagnosed by the treating physician and confirmed by comprehensive study staff chart review.

Group 0 sample size Number of subjects in the control (unexposed) group: 81

Group 1 sample size Number of subjects in the case (exposed) group: 81

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Random Forest Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.2

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 1

Matched on Factors on which subjects have been matched on in a case-control study: age, Matched on: "disease status" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.disease status

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: diet, Confounders controlled for: "symptoms" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.symptoms, Confounders controlled for: "mode of delivery" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.mode of delivery, Confounders controlled for: "age at visit" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.age at visit, Confounders controlled for: "Probiotics use in the first year of life" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Probiotics use in the first year of life

Alpha Diversity

Richness Number of species: increased

Signature 1

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Curated date: 2023/10/10

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Peace Sandy

Source: 2A

Description: Differences in infant microbiome in children who developed FPIAP compared to those who did not using relative abundance.

Abundance in Group 1: increased abundance in Infants diagnosed with food protein-induced allergic proctocolitis (FPIAP)

NCBI	Quality Control	Links
Bacteroides
Bifidobacterium
Blautia
Clostridiaceae bacterium
Clostridium
Enterobacteriaceae
Haemophilus
Lachnospiraceae
Lactobacillus
Parabacteroides
Ruminococcus
Streptococcus
Veillonella
unclassified Enterobacteriaceae
Clostridiales bacterium 1_7_47FAA

Revision editor(s): Tolulopeo, Peace Sandy